BRD4
From Wikipedia, the free encyclopedia
Bromodomain-containing protein 4 is a protein that in humans is encoded by the BRD4 gene.[1][2]
The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human RING3 protein, a serine/threonine kinase. Each of these proteins contains two bromodomains, a conserved sequence motif which may be involved in chromatin targeting. This gene has been implicated as the chromosome 19 target of translocation t(15;19)(q13;p13.1), which defines the NUT midline carcinoma. Two alternatively spliced transcript variants have been described.[2]
Interactions
BRD4 has been shown to interact with RFC2,[3] RFC3,[3] RFC1,[3] RFC4[3] and RFC5.[3]
Structures
Several 3D structures of individual domains of BRD4 have been solved, some in complex with inhibitor molecules
References
- ↑ Dey A, Ellenberg J, Farina A, Coleman AE, Maruyama T, Sciortino S, Lippincott-Schwartz J, Ozato K (September 2000). "A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)-to-M transition". Mol Cell Biol 20 (17): 6537–49. doi:10.1128/MCB.20.17.6537-6549.2000. PMC 86127. PMID 10938129.
- ↑ 2.0 2.1 "Entrez Gene: BRD4 bromodomain containing 4".
- ↑ 3.0 3.1 3.2 3.3 3.4 Maruyama, Tetsuo; Farina Andrea, Dey Anup, Cheong JaeHun, Bermudez Vladimir P, Tamura Tomohiko, Sciortino Selvaggia, Shuman Jon, Hurwitz Jerard, Ozato Keiko (September 2002). "A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase". Mol. Cell. Biol. (United States) 22 (18): 6509–20. doi:10.1128/MCB.22.18.6509-6520.2002. ISSN 0270-7306. PMC 135621. PMID 12192049.
Further reading
- French CA, Miyoshi I, Aster JC et al. (2001). "BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19)". Am. J. Pathol. 159 (6): 1987–92. doi:10.1016/S0002-9440(10)63049-0. PMC 1850578. PMID 11733348.
- Maruyama T, Farina A, Dey A et al. (2002). "A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase". Mol. Cell. Biol. 22 (18): 6509–20. doi:10.1128/MCB.22.18.6509-6520.2002. PMC 135621. PMID 12192049.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- French CA, Miyoshi I, Kubonishi I et al. (2003). "BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma". Cancer Res. 63 (2): 304–7. PMID 12543779.
- Grimwood J, Gordon LA, Olsen A et al. (2004). "The DNA sequence and biology of human chromosome 19". Nature 428 (6982): 529–35. doi:10.1038/nature02399. PMID 15057824.
- You J, Croyle JL, Nishimura A et al. (2004). "Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes". Cell 117 (3): 349–60. doi:10.1016/S0092-8674(04)00402-7. PMID 15109495.
- Colland F, Jacq X, Trouplin V et al. (2004). "Functional proteomics mapping of a human signaling pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
- Beausoleil SA, Jedrychowski M, Schwartz D et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
- Farina A, Hattori M, Qin J et al. (2004). "Bromodomain protein Brd4 binds to GTPase-activating SPA-1, modulating its activity and subcellular localization". Mol. Cell. Biol. 24 (20): 9059–69. doi:10.1128/MCB.24.20.9059-9069.2004. PMC 517877. PMID 15456879.
- Baxter MK, McPhillips MG, Ozato K, McBride AA (2005). "The mitotic chromosome binding activity of the papillomavirus E2 protein correlates with interaction with the cellular chromosomal protein, Brd4". J. Virol. 79 (8): 4806–18. doi:10.1128/JVI.79.8.4806-4818.2005. PMC 1069523. PMID 15795266.
- Haruki N, Kawaguchi KS, Eichenberger S et al. (2006). "Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro". J. Med. Genet. 42 (7): 558–64. doi:10.1136/jmg.2004.029686. PMC 1736105. PMID 15994877.
- Schweiger MR, You J, Howley PM (2006). "Bromodomain protein 4 mediates the papillomavirus E2 transcriptional activation function". J. Virol. 80 (9): 4276–85. doi:10.1128/JVI.80.9.4276-4285.2006. PMC 1472042. PMID 16611886.
- Wu SY, Lee AY, Hou SY et al. (2006). "Brd4 links chromatin targeting to HPV transcriptional silencing". Genes Dev. 20 (17): 2383–96. doi:10.1101/gad.1448206. PMC 1560413. PMID 16921027.
- You J, Srinivasan V, Denis GV et al. (2006). "Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen interacts with bromodomain protein Brd4 on host mitotic chromosomes". J. Virol. 80 (18): 8909–19. doi:10.1128/JVI.00502-06. PMC 1563901. PMID 16940503.
- Sénéchal H, Poirier GG, Coulombe B et al. (2007). "Amino acid substitutions that specifically impair the transcriptional activity of papillomavirus E2 affect binding to the long isoform of Brd4". Virology 358 (1): 10–7. doi:10.1016/j.virol.2006.08.035. PMID 17023018.
- Olsen JV, Blagoev B, Gnad F et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
- Abbate EA, Voitenleitner C, Botchan MR (2007). "Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a peptide that ablates HPV chromosomal association". Mol. Cell 24 (6): 877–89. doi:10.1016/j.molcel.2006.11.002. PMID 17189190.
- Schweiger MR, Ottinger M, You J, Howley PM (2007). "Brd4-independent transcriptional repression function of the papillomavirus e2 proteins". J. Virol. 81 (18): 9612–22. doi:10.1128/JVI.00447-07. PMC 2045424. PMID 17626100.
- Bisgrove DA, Mahmoudi T, Henklein P, Verdin E (2007). "Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription". Proc. Natl. Acad. Sci. U.S.A. 104 (34): 13690–5. doi:10.1073/pnas.0705053104. PMC 1959443. PMID 17690245.
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